Using B-cell hybrids developed during our research, it has been possible to study several events that occur following the binding of an antigen to membrane-associated receptors. The hybrids synthesize both a membrane-associated form of immunoglobulin (mIg) and a secreted form of immunoglobulin (sIg). The mIg and sIg are distinguished by molecular weight differences. Both Ig forms are specific for the hapten phthalate and express common isotypes and idiotype. Following the cross-linking of the mIg with multivalent hapten ligands, the resultant receptor-ligand complexes are aggregated and internalized. The cross-linked receptors appear to be linked or associated with a large cytoplasmic protein (alpha-spectrin). This is based upon the observation (with immunofluorescence) that the cross-linked receptors migrate coincidentally with the high molecular weight cytoskeletal protein (alpha-spectrin). After antigen-induced clearance of receptors, the cells reexpress receptors within 4 hrs. Multiple cycles of antigen-induced receptor clearance and reexpression take place in the absence of protein synthesis. We conclude that a presynthesized pool of receptors exists within the cytoplasm and that these antigen-specific receptors are reutilized. These findings and continued studies provide significant information about how B cells bind and internalize specific ligands, requisite events in the process of activation and differentiation. One practical aspect of this work relates to the development of several new cancer drug delivery systems that are all based upon the use of antibody-drug or antibody-liposome drug conjugates. Some of the major unresolved questions are how, or if, these antibody-drug complexes are internalized, where do they travel within the cell, and what is their ultimate fate? Hybrids also have been exploited to study the process of immunoglobulin secretion. It is apparent from these studies that sIg is released from the cell at a restricted domain in the plasma membrane. These studies are being pursued both biochemically and ultrastructurally. (LB)